Our goal is to provide a coherent mechanistic explanation for how the NaCl cotransporter (NCC) of the renal distal tubule is regulated in response to variation in potassium diet. Such a response is thought to play a central role in switching the mineralocorticoid hormone response of the kidney to either conserve sodium or excrete potassium, depending on whether aldosterone is induced by a change in dietary sodium or potassium. It is well known that NCC is up regulated by aldosterone in states of low Na diet and intravascular volume depletion. Remarkably, however, NCC is suppressed in high aldosterone states that accompany hyperkalemia or following ingestion of a potassium-rich diet. Perhaps even more surprising, NCC is activated following ingestion of a low potassium diet when aldosterone is kept low to minimize potassium secretion. While it is widely believed that the WNK-SPAK network of kinases functions as a physiological switch to coordinate renal Na reabsorption and potassium secretion, current models fail to explain how NCC can be regulated by potassium diet independent of aldosterone. Our goal is to resolve this riddle with a new and testable model that explains how regulation of NCC can become uncoupled from aldosterone signals. We use animal models to test specific predictions of our proposed model to demonstrate that the mechanism is functionally relevant in the in vivo kidney. We then use the mpkDCT cell model and methods that manipulate critical components to carry out mechanistic tests of the model's predictions. Our aim is to fill a fundamental gap in the understanding of how renal Na transport is coordinated with potassium diet. We expect to answer the following specific questions: 1) What is the role of SPAK and WNK4 phosphorylation in activation of NCC in the kidney? 2) How do WNKs modulate SPAK-Dependent regulation of NCC?